(a) Technical Field
The present invention relates to a novel medicinal use of pyrazolopyrimidine compounds having superior effect as serotonin 5-HT2C receptor ligand thus being useful for the prevention and treatment of central nervous system (CNS) diseases.
(b) Background Art
Receptors of serotonin, a neurotransmitter, are known to be involved in various mental disorders (e.g., depression, aggressiveness, seizure, compulsive neurosis, psychosis, schizophrenia and suicidal tendency), neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease and Huntington's chorea), sitophobia, bulimia, alcoholism-related disorders, cerebral vascular accidents and migraine [Meltzer, Neuropsychopharmacology, 21:106 S-115S (1999); Barnes & Sharp, Neuropharmacology, 38:1083-1152 (1999); Glennon, Neurosci. Biobehavioral Rev., 14:35 (1990)].
Serotonin 5-hydroxytryptamine (5-HT) receptors are widely distributed throughout the bodies of humans and animals and play an important role in physiological and behavioral functions. So far, about 15 genetically different 5-HT receptor subtypes have been cloned. Each subtype exhibits unique distribution and shows various preference and relationships for different ligands. Recently, 5-HT receptor subtypes have been shown to be related to the causes of diseases such as hypertension, thrombus, migraine, vasospasm, ischemia, depression, anxiety, psychosis, schizophrenia, sleep disorder and appetite disorder. Among serotonin 5-HT2 family, 5-HT2A and 5-HT2B receptors are abundant in peripheral nervous system, whereas serotonin 5-HT2C receptors are abundant in central nervous system, especially in brain. Therefore, it has been expected that a novel ligand acting effectively on serotonin 5-HT2C would be useful as a new drug for the treatment of CNS diseases such as obesity, depression, anxiety, and withdrawal symptoms due to drug abuse.
WO2009/023978 confirms the inhibitory activity of pyrazolo[3,4-D]pyrimidine against EphB4 receptor tyrosine kinase, and based on this, it teaches that the compound is effective as a therapeutic agent for the treatment of proliferative diseases associated with the protein kinase activity. However, there has been no report yet that discloses the superior activity of pyrazolopyrimidine as a ligand acting on serotonin 5-HT2C to show its effectiveness in the prevention and treatment of CNS diseases such as withdrawal symptoms due to obesity, depression, anxiety, and drug abuse.